PHYSIOLOGY

As you climb above sea level, atmospheric (barometric) pressure
drops with a parallel decrease in the amount of oxygen available at the
blood/air interface in the lung alveolus. Hypoxia (a low blood oxygen level)
results and limits the maximum amount of oxygen that can be delivered to the
muscle cells to support aerobic physical work. Although the heart rate (and
cardiac output) increase to deliver more blood (with less oxygen per ml) to
the muscle cell, complete compensation does not occur and the maximal
aerobic ability (VO2 max.) is reduced by approximately 1%
for every 100 meters (~ 300 feet) above 4500 feet. This change can be
measured in the performance of highly trained athletes at altitudes as
low as 1500 feet above sea level.

The body implements a number of adaptive changes (acclimatization)
which include a higher ventilation (respiratory or breathing) rate and a higher
blood lactate level for any level of sub-maximal exercise to offset the lower
blood oxygen levels as the elevation above sea level increases. Both of these
increase an individual's sensation of dyspnea (shortness of breath) and
fatigue. Acclimatization responses begin immediately and may take 4 to 6
weeks to reach their maximal effectiveness - specifically an increase in red
blood cell mass.

In addition to a decrease in maximal aerobic capacity, the symptoms of
acute mountain sickness (AMS) affect, to varying degrees, all travelers to
elevations greater than 5280 feet. In a small percentage of those climbing to
this altitude, AMS can lead to high-altitude pulmonary edema (HAPE) and/or
high-altitude cerebral edema (HACE). Symptoms of AMS range from a
combination of headache, insomnia, anorexia, nausea, and dizziness,to
more serious manifestations, such as vomiting, dyspnea, muscle weakness,
oliguria, peripheral edema, and retinal hemorrhage.

Although the primary cause of symptoms at altitude is the reduced
oxygen content (of the air and as a result the blood) at high altitudes, the
physiologic pathway leading from hypoxia to AMS (and its sequelae) remains
unclear. Tips on self-diagnosis and symptom
recognition are critical elements to include in educating those who are
contemplating a trip to high altitudes.

Short term (days) physiologic adjustments to altitude

The most immediate response to altitude is the hyperventilation that occurs
in response to the decrease in blood (arterial) oxygen levels (a significant
symptom above 2000 meters). This increased respiratory rate can remain elevated
for up to a year at altitude. The degree of this hyperventilation response
varies from individual to individual - those with a strong hypoxic drive will
perform exercise tasks better at altitude than those with a blunted ventilatory
response.

A second is an increase in resting heart rate and, as a result, cardiac output.
The increase in blood flow at the muscle cell level compensates for
the decrease in blood oxygen concentration with the total amount of oxygen being
delivered to the muscles in a resting state being unchanged. However, the fact
that there is always a lower blood oxygen concentration means that even with
the compensatory increase in heart rate and blood flow, the level of exercise
at which oxygen demands are unmet and metabolism shifts to anaerobic (VO2 max.
has been reached) will always be less than at sea level.

Long term (weeks) adjustments to altitude

Hyperventilation and an increased cardiac output are the immediate
response to limit the effects of altitude on physical performance.

With time, a change in the body's acid-base balance counters the effects of
a chronically lower blood CO2 from hyperventilation (respiratory alkalosis),
but does not affect physical performance to any significant degree.

An increase in the blood hemoglobin (hematocrit) level over 3
to 4 weeks increases the oxygen
carrying capacity of the blood and is the most important of all the performance
adaptations to altitude. The result is that every milliliter of blood
that moves through the muscle capillaries will be able to deliver an
increased amount of oxygen compared to the same volume of blood with a
sea level hematocrit.

Finally, there are cellular changes that favor oxygen delivery to the muscle
cell. The capillary concentration (very small blood vessels) in skeletal
muscle is increased in animals living at altitude compared to those at sea
level, and muscle biopsies in acclimatized men have shown an increase
in myoglobin, mitochondria, and the metabolic enzymes necessary for aerobic
energy production. Taken together, these changes improve the efficiency of oxygen
delivery to the muscle cell as well as the extraction of blood oxygen at the
muscle cell level.

These adaptations are sufficient to restore maximum aerobic exercise capacity
(VO2max) to NEAR sea level values at altitudes up to 2500 meters (7500 feet).
At higher elevations, acclimatization will never restore VO2 max. to what is
possible at sea level.

Not all the changes that occur with acclimatization are favorable to
improve athletic performance in the face of a decrease in available oxygen.
One notable negative is the loss of lean body mass and body fat that occurs
with long term exposure to high altitudes. The result is a decreased
maximum potential for athletic performance because of decreased muscle
mass.

The time course of acclimatization

As mentioned, the ventilatory response begins immediately upon climbing to
altitude from sea level.

Hyperventilation changes the blood acid base
balance (with a respiratory alkalosis) which in turn stimulates the kidneys
to excrete bicarbonate to compensate. This renal compensatory response
takes about a week.

The sympathetic nervous system is activated almost immediately with an
increase in both sympathetic nerve activity and an increase in blood
epinephrine levels - resulting in an increase in heart rate and cardiac
output to maintain tissue oxygen delivery at near sea level values. By
two to three weeks, blood flow returns toward sea level values as muscle oxygen
delivery improves as a result of the other compensatory mechanisms.

The hematocrit level begins to increase within 24 to 48 hours as a
result of a reduction in plasma volume, not an increase in overall red cell
mass. Erythropoietin levels increase within hours, peak at about 48 hours,
and remain elevated for 1 to 2 weeks. They in turn stimulate the bone marrow
to increase production and the total circulating red cell mass increases
slowly (and may take several years to reach levels equal to natives living
permanently at these altitudes).

The vast majority of these metabolic changes are complete by 3 to 4 weeks
at altitude, but the structural changes (capillary density, mitochondrial
number) will take weeks to months.

How about iron?

There was a recent article that suggested that iron might be of benefit for those
competing at altitude. But if you read the detail, it really is about iron helping
the performance of anyone who is iron deficient (at sea level or altitude). It is
a great example of the way valid scientific
results can be mis interpreted leading to the abuse of supplements - as well as exposing
users to potential toxicity along the way (elemental iron is not a benign supplement).

This was a pretty strong claim so I thought I'd look for more details
in the original article in PLOS.
Although the PLOS article was quoted as supporting improved athletic performance at altitude with
iron supplements, as far as I can determine it only found that IRON DEFICIENT athletes
incorporate more substrate (iron) into their blood cells if they were given supplements - which
makes sense. They need iron (even at sea level as they are iron deficient), so given iron plus the
stimulus of altitude, it is only reasonable to assume that they will absorb more of it. And
as iron is in many enzymes (along with iron in blood cells), one might also expect some performance
improvement (non heme level related) in the iron deficient athletes as well. And of course there is
no evidence that the iron deficient group actually improved performance - only that the blood cell mass
increased and thus it was assumed they would perform better as well.

So unless you are iron deficient (have a low ferritin), iron will not help your performance (at altitude
or sea level), and if you have adequate iron stores, there are risks of iron overload and toxicity
with unneeded supplements.

Viagra (sildenafil)- a reasonable option for a subset of athletes who
suffer from altitude.

This article
suggests that there may be an option to counteract the negative performance effects of
altitude in some athletes - Viagra. In this figure
we see that a subgroup of athletes at altitude (responders) experienced a significant decrement
in performance which was then corrected by sildenafil (bringing them back to the level of performance of
the non-responders to the drug). We know that the endogenous production of nitric oxide (NO) is elevated
in populations living at high altitudes, which helps these people avoid hypoxia by
aiding in pulmonary vasculature vasodilation. The findings in this paper
suggest that a sub group (very possibly those prone to the effects of altitude sickness - headache,
pulmonary edema, nausea) may be those that benefit. In this subgroup, it is possible (speculation)
that the sildenafil reverses the metabolic shortcomings in endogenous NO production that lead to their
initial sub par performance.

Viagra increase the effects of NO in erectile dysfunction by increasing the sensitivity to NO released with
sexual stimulation from nerve endings and endothelial cells in the corpus cavernosum of the
penis. The NO then stimulates an enzyme to convert guanosine triphosphate (GTP) into cyclic guanosine
monophosphate (cGMP). And it is the cGMP that causes the smooth muscle of the arteries
in the penis to relax, in turn allowing an inflow of blood leading to an erection.
cGMP is broken down and back to the inactive GMP by a second enzyme - phosphodiesterase type 5 (PDE5).
Men who suffer from erectile dysfunction often produce too little endogenous NO and the small amount of cGMP
they subsequently produce is eliminated quickly (the same absolute rate of degradation, but less total cGMP to be
metabolized so the level of total cGMP decreases at a faster rate). Thus it doesn't accumulate
and lead to the hoped for vasodilation effect. Sildenafil (Viagra) works by inhibiting the
enzyme PDE5. This means that cGMP is not hydrolyzed as fast, accumulates to higher levels, and
as a result is present for a longer time to act to allow the smooth muscle to relax. Sildenafil is a potent and highly selective inhibitor of PDE5.

If you suffer disproportionately from the effects of altitude (nausea, headaches), Viagra
may eliminate the metabolic changes that are putting you at a performance disadvantage. And may "level the playing field"
for a competitive event.

ALTITUDE AS A TRAINING AID

Do the adaptive mechanisms described above compensate for the decrease in
oxygen available at altitude. The answer is NO. Even with acclimatization,
for any level of activity, the proportion of the energy supplied by anaerobic
metabolism (versus oxygen supported or aerobic pathways) increases
and as a result performance suffers.

Does anaerobic (i.e. hypoxic) exercise at altitude provide a training benefit?
This is controversial, but controlled studies in trained athletes have not
confirmed a benefit for hypoxic exercise WITHOUT CONCOMITANT
ACCLIMATIZATION.

And the direct effects of interval training to stress and improve an athlete's
maximum aerobic capacity (VO2 max.) at altitude deteriorate with training at
elevation as a result of the inability to achieve a VO2 max. that is
comparable to what is possible at sea level. During
interval work outs, speed, oxygen uptake, heart rate, and lactate levels
are all lower than those from lower altitudes suggesting that interval
training is best performed as near sea level as possible.

Does exercise training at altitude improve sea level performance?

Many scientists, athletes, and coaches have been intrigued by the similarities
of altitude acclimatization and training effects. Does
living and training at altitude (with the associated changes in red
cell mass and cellular changes in mitochondria, etc.) lead to an increase
in the maximal aerobic exercise capacity (VO2 max.) upon return to sea level?
The answer is "it depends". It is the net balance of the
benefits of the acclimatization effects countered by the negatives of a
reduction in training intensity and resulting deconditioning (in an oxygen
limited environment) that are the ultimate determinate of the outcome of
altitude training in endurance athletes.
Controlled studies have NOT shown any advantage of TRAINING at altitude
compared to a similar TRAINING program (the same absolute VO2 max. being
achieved at both altitudes) at sea level.

Are there any strategies that can use altitude to benefit a training
program?

The answer to this question is YES. But it requires balancing the
acclimatization benefits of an increased red cell mass from living at
altitude (one must be at altitude for more than 12 hours a day to
maintain an increase erythropoietin level) while maximizing the VO2 max.
achievable in training equivalent to that possible at sea level.

How high must one live to maximize acclimatization? An altitude of 2500 to
2800 meters maintains a balance between stimulating erythropoietin and
minimizing the effects of acute mountain sickness that occur with increasing
frequency at higher elevations.

How long should one live at altitude to maximize benefits?? At least 3 to
4 weeks.

How long will the acclimatization effects last? Based on actual performance
studies, 2 to 3 weeks at most before they begin to reverse.

And the optimal training altitude? Although this should be individualized
as some athletes do quite well maintaining a high VO2 max training at high
altitudes, the general rule is to train as close to sea level as possible,
preferably below 1500 meters.

So it is the balance between acclimatization and deconditioning that gives
the personalized answer for each individual athlete. A few can maintain a
high training VO2 max. even while training at altitude enabling them to live
at altitude and train there as well. But the vast majority need to descend
to train several times a week or face a competitive disadvantage from
deconditioning.

THE BOTTOM LINE

Altitude can be used to improve sea level performance. But it needs to be
used correctly. Its advantages are related to acclimatization effects i.e.
an increase in the red cell mass from 2 to 3 weeks at altitude. The same
benefits could be gained from using injections of erythropoietin if it were
not a banned substances (and one with some health risks as well from
overzealous use and exceedingly high hematocrits). Blood doping has the
same effects. And it has been suggested that living (or sleeping for more
than 12 hours a day) in a high altitude chamber or using nitrogen houses as
the Scandinavians have proposed (and utilized) may have the same beneficial
effect.

But to maximize the benefits of the altitude effect, training (i.e.
absolute VO2 max. achievable) should be near sea level. Some
athletes can train at altitude and pull this off, but the majority
will need to do interval training at least twice a week at sea level oxygen
levels to avoid the disadvantages of deconditioning (and a lower personal VO2max
with time).

Altitude effects on performance are a complex issue, but are best
summarized in the simple mantra:

"LIVE HIGH, TRAIN LOW".

Is there any way to avoid the hassles of traveling to a lower elevation to
train - gaining the advantages of the hypoxia of altitude to acclimatize
during the majority of your day (and while sleeping at night) while
maintaining a high level training program?

The Scandinavians reportedly live in a "nitrogen" house which
lowers the ambient oxygen level during sleep and the portion of the day
they spend there (and training is as easy as stepping out the door), while
others have suggested sleeping in an altitude chamber. Another option that
seemed to make sense to the author was living at altitude and using
supplemental oxygen while training to raise the amount of oxygen available
to the alveoli in the lung and maximizing VO2max achievable during training
sessions. This question was addressed to Dr. Ben Levine who has done the
majority of the work leading up to the high-low theory of
training.

His response:

Dear Dr. Rafoth,

Thanks for your note. You are absolutely right that an alternative to
travel for high-low is training high with supplemental O2. In fact, this is
exactly the tack taken by US Cycling and US Swimming at Colorado
Springs. It is a bit cumbersome, but as long as the workouts can be
reproduced, will work fine.

Ben Levine

COMPETITION AT ALTITUDE

What should an athlete do to prepare for competition at altitude ?

For endurance events, if it is possible, adequate time should be allowed to complete
acclimatization - 2 to 3 weeks. The longer one waits, the more
deconditioning of the VO2 max. that occurs. Returning to sea level to do
interval training several times a week to minimize the deconditioning effect
would be a definite advantage but is usually impractical.

Is it worth it, three weeks at altitude if one cannot return to sea level to
maintain their conditioning? One article suggests the benefit (aside from acclimatization
to avoid acute mountain sickness) gets one very little - maybe
a 1% improvement. Thus it is very possible that for the majority of us mortals, 3 to 5 days
is just enough to balance the positives of acclimatization against the negatives of detraining while
waiting to acclimate.

For sprints (400 meters or less) most of the energy for muscular activity
is oxygen independent (anaerobic) and acclimatization will not be of any
benefit. But the lower air resistance at altitude will decease race times -
which is why the 400 meter events were very fast in Mexico City in 1968 but
the longer 1500 meter results were slower than at sea level.

A major concern would be Acute Mountain Sickness. The
rider needs to accept that there will be an inevitable decrease in
VO2max (see above) and no special training program that will blunt this
effect of altitude on performance.

Preventive strategies might include allowing 2 days of acclimatization
before engaging in strenuous exercise at high altitudes, avoiding alcohol,
and increasing fluid intake. A high-carbohydrate, low-fat, low-salt
diet may aid in preventing the onset of AMS.

Although slow ascent is the preferred approach to avoiding AMS, there are
times when this is impractical (plane connections to the start of a ride,
emergency situations). In those cases, there are medications available
that can decrease the chances of developing AMS. Acetazolamide (250 mg twice
daily or 500 mg slow release once daily), taken before and during, ascent is
recommended by many physicians although dexamethasone (4 mg, 4 times daily)
has been shown to be of equal effectiveness. And in one study, those on
acetazolamide actually had more symptoms of nausea at low altitudes
(where AMS was not an issue) than a placebo group. Nausea was not a problem
for those using dexamethasone, and indeed a mild euphoria was often
reported. The usual recommendation for both medications is to start
24 hours before going to altitude and then continuing for 48 hours after
starting the ascent. By that time, normal adaptive mechanisms should have
had time to take over.

As dexamethasone is faster acting than acetazolamide, some authorities
suggest taking the dexamethasone along, but starting it only when and if
symptoms develop. As severe AMS is uncommon, this eliminates the
inconvenience (and possible drug allergy or intolerance) of a medication
that might not be needed.